Voriconazole Pharmacokinetics in Children With Gastrointestinal Graft Versus Host Disease

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Phillip Brian Smith, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00792246
First received: November 13, 2008
Last updated: November 9, 2012
Last verified: November 2012
  Purpose

Determine how much voriconazole is absorbed when the product is given by mouth to children with extensive graft versus host disease after a stem cell transplantation and determine the correct dosing of voriconazole in this population.

Hypothesis: Children with gastrointestinal graft versus host disease will have decreased absorption of oral voriconazole and require higher doses of voriconazole in order to prevent or treat fungal infections.


Condition Intervention Phase
Graft Versus Host Disease
Stem Cell Transplantation
Drug: voriconazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Define the Pharmacokinetics of Oral Voriconazole in Children With Extensive Gastrointestinal Graft Versus Host Disease

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Reduced bioavailability of oral voriconazole in pediatric patients status post stem cell transplantation with gastrointestinal graft versus host disease [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics(including clearance, maximum concentration, area under the time concentration curve, and half life) of voriconazole in pediatric patients status post hematopoietic stem cell transplantation. [ Time Frame: one year ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: December 2008
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: graft versus host disease
Patients receiving oral voriconazole will be switched to intravenous voriconazole. Pharmacokinetics will be determined after each formulation.
Drug: voriconazole
Voriconazole formulation will be changed from oral to intravenous at the same dose the subject is currently receiving per standard of care.
Experimental: No graft versus host disease
Patients receiving oral voriconazole will be switched to intravenous voriconazole. Pharmacokinetics will be determined after each formulation.
Drug: voriconazole
Voriconazole formulation will be changed from oral to intravenous at the same dose the subject is currently receiving per standard of care.

Detailed Description:

Disseminated fungal infections are a leading cause of mortality in children who receive hematopoietic stem cell transplantation (SCT). Therefore, children routinely receive prophylactic and empirical antifungal therapy after SCT. The most commonly used antifungal agent in this population is voriconazole. Voriconazole can be given via intravenous or oral routes and children who are post SCT are routinely switched from the intravenous to oral formulation at the time of hospital discharge. However, the absorption and systemic exposure of oral voriconazole has not been well-described in children. Furthermore, many children who undergo transplantation develop gastrointestinal graft versus host disease and this likely impacts oral absorption. The magnitude of effect resulting from graft versus host disease on absorption of voriconazole and subsequent blood concentrations in children is unknown. Thus children with graft versus host disease are at a particularly high risk of inadequate absorption with subsequent sub-therapeutic levels of voriconazole. They may need higher or more frequent dosing to achieve therapeutic levels. The purpose of my research project is to define the pharmacokinetics of oral voriconazole and establish dosing guidelines in children following SCT.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≤ 18 years, sufficient venous access to permit administration of voriconazole, ability to take oral medications, written informed consent provided by the parent or legally authorized representative, and Grade II or higher (extensive) gastrointestinal graft versus host disease for those patients in the graft versus host disease patient subset.

Exclusion Criteria:

  • History of anaphylaxis attributed to voriconazole or other triazole compounds, any concomitant condition, which in the opinion of the investigator would preclude a patient's participation in the study, or previous participation in this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00792246

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Phillip Brian Smith
Investigators
Principal Investigator: P Brian Smith, MD Duke Unviersity Medical Center
  More Information

No publications provided

Responsible Party: Phillip Brian Smith, Associate Professor of Pediatrics, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00792246     History of Changes
Other Study ID Numbers: Pro00004318
Study First Received: November 13, 2008
Last Updated: November 9, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Duke University:
pharmacokinetics
pediatric
bioavailability

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Voriconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014